{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:22:30Z","timestamp":1792668150173,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T00:00:00Z","timestamp":1486512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>In the pharmaceutical industry risk assessments of chronic cardiac safety liabilities are mostly performed during late stages of preclinical drug development using <jats:italic>in vivo<\/jats:italic> animal models. Here, we explored the potential of human induced pluripotent stem cell\u2010derived cardiomyocytes (hiPS\u2010CMs) to detect chronic cardiac risks such as drug\u2010induced cardiomyocyte toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Video microscopy\u2010based motion field imaging was applied to evaluate the chronic effect (over 72\u00a0h) of cardiotoxic drugs on the contractile motion of hiPS\u2010CMs. In parallel, the release of cardiac troponin I (cTnI), heart fatty acid binding protein (FABP3) and N\u2010terminal pro\u2010brain natriuretic peptide (NT\u2010proBNP) was analysed from cell medium, and transcriptional profiling of hiPS\u2010CMs was done at the end of the experiment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Different cardiotoxic drugs altered the contractile motion properties of hiPS\u2010CMs together with increasing the release of cardiac biomarkers. FABP3 and cTnI were shown to be potential surrogates to predict cardiotoxicity in hiPS\u2010CMs, whereas NT\u2010proBNP seemed to be a less valuable biomarker. Furthermore, drug\u2010induced cardiotoxicity produced by chronic exposure of hiPS\u2010CMs to arsenic trioxide, doxorubicin or panobinostat was associated with different profiles of changes in contractile parameters, biomarker release and transcriptional expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We have shown that a parallel assessment of motion field imaging\u2010derived contractile properties, release of biomarkers and transcriptional changes can detect diverse mechanisms of chronic drug\u2010induced cardiac liabilities in hiPS\u2010CMs. Hence, hiPS\u2010CMs could potentially improve and accelerate cardiovascular de\u2010risking of compounds at earlier stages of drug discovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v174.21\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v174.21\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13713","type":"journal-article","created":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T19:12:34Z","timestamp":1484680354000},"page":"3766-3779","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Chronic drug\u2010induced effects on contractile motion properties and cardiac biomarkers in human induced pluripotent stem cell\u2010derived cardiomyocytes"],"prefix":"10.1111","volume":"174","author":[{"given":"Ivan","family":"Kopljar","sequence":"first","affiliation":[{"name":"Preclinical Development and Safety, Discovery Sciences, Janssen Research and Development Janssen Pharmaceutica NV  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